Method of manufacturing a neural interface probe employing amorphous silicon carbide

ABSTRACT

Manufacturing a neural interface device. Forming a neural interface probe of an implantable microelectrode body. PECVD a first amorphous silicon carbide insulation layer, forming a thin film metal trace and interface pad on the first layer, the pad on a portion of the trace. PECVD a second amorphous silicon carbide insulation layer on the first layer and covering the trace and the pad. Forming an opening in the second layer to expose the pad to an ambient environment. Patterning the first and second layers to define the neural interface probe. The probe has a rectangular cuboid shape, a cross-sectional area perpendicularly transverse to a long axis length of the probe and through any perpendicularly transverse cross-section along the long axis length is less than about 50 microns. The layers are the principle material of construction of the probe.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.16/015,878, filed Jun. 22, 2018, which claims benefit of U.S.Provisional Application Ser. No. 62/523,825, filed by Gardner, et al. onJun. 23, 2017, entitled “NEURAL INTERFACE PROBE WITH AMORPHOUS SILICONCARBIDE INSULATION,” commonly assigned with this application andincorporated herein by reference

GOVERNMENT LICENSE RIGHTS

This invention was made with Government Support under Contract No.NS090454 awarded by the National Institutes of Health. The governmenthas certain rights in this invention.

TECHNICAL FIELD

This application is directed, in general, to a neural interface deviceand, more specifically, to an implantable body of the device and methodsof manufacturing the same.

BACKGROUND

Chronically implanted microelectrode arrays (MEAs) for recordingextracellular neural activity are central to scientific studies ofneural circuit function. In clinical applications employingbrain-machine and brain-computer interfaces such MEAs are essential forrecording electrical neural signals. Limitations to achievingchronically stable neural recordings with existing microelectrode arraysinclude reactive tissue foreign body response that encapsulates theelectrodes and kills or damages neurons, and, a decline in deviceperformance often characterized by a progressive decrease in neuralsignal amplitude and loss of viable recording channels. Likewise,chronically implanted MEAs are employed in clinical applicationsrequiring the delivery of therapeutic electrical stimulation. Suchstimulating MEAs have the same limitations as recording MEAs.

SUMMARY

One embodiment of the invention is a neural interface device thatcomprises an implantable microelectrode body. The implantablemicroelectrode body includes a neural interface probe, which includes athin film metal trace connected to an interface pad and an amorphoussilicon carbide insulation. The amorphous silicon carbide insulationsurrounds the thin film metal trace to form an outside surface of theneural interface probe. The interface pad is exposed to an ambientenvironment of the neural interface probe through an opening in theamorphous silicon carbide insulation.

Any such embodiments of the neural interface probe can have arectangular cuboid shape, and a cross-sectional area perpendicularlytransverse to a long axis length of the probe and through anyperpendicularly transverse cross-section along the long axis length canbe less than about 50 microns². For any such embodiments of the neuralinterface probe, the amorphous silicon carbide insulation can be theprinciple material of construction of the probe such that at least about85 percent of a total area any one of the cross-sections along the longaxis length is composed of the amorphous silicon carbide insulation.

Any such embodiments of the neural interface probe can have a bucklingresistance of least about 15 N-μm². Embodiments of the neural interfaceprobe can have a height and a breadth defining the cross-sectional areathat provides the probe with a minimum area-moment-of-inertia of thecross-section of at least about 50 μm⁴. In some such embodiments, atleast one of the height or the breadth has a maximum value of about 20μm, and preferably a maximum value of 10 □m. For any such embodiments ofthe neural interface probe, any one of the perpendicularly transversecross-sections along the long axis length can have a totalcross-sectional area of about 100 μm² or less. For any such embodimentsof the neural interface probe, for the perpendicularly transversecross-sections intersecting the thin film metal trace or the interfacepad, a ratio of a cross-sectional area of the thin film metal trace to across-sectional area of the amorphous silicon carbide insulation is avalue in a range from about 1:40 to about 10:40, and in someembodiments, in a range from about 1:40 to less than 4:40, and in someembodiments from about 1:40 to about 2:40.

For any such embodiments, the thin film metal trace can include one ormore discrete layers composed of titanium, chromium, tungsten, gold,iridium, platinum, or palladium and the interface pad can includetitanium nitride, iridium oxide, porous platinum, orpoly(ethylenedioxythiophene). In some embodiments, the metal layers arepartially intermixed to improve adhesion. For any such embodiments, theamorphous silicon carbide insulation of the probe can have an elasticmodulus of about 300 GPa. For any such embodiments, the neural interfaceprobe can consist essentially of the thin film metal trace the interfacepad, and the amorphous silicon carbide insulation.

Any such embodiments of the implantable microelectrode body can furtherinclude a connection body surrounded by the amorphous silicon carbideinsulation. The thin film metal trace of the neural interface probe canextend to a communication circuit of the connection body, and, thecommunication circuit can include an electrical contact pad directlyconnected to the thin film metal trace. In some such embodiments, theelectrical contact pad can be connected, by a second opening in theamorphous silicon carbide insulation, to a wire lead or to a metal traceon a flexible ribbon cable to carry electrical signals via the wire leador flexible ribbon cable between the interface pad and a non-implantedrecording or stimulating apparatus of the device. In some suchembodiments, the electrical contact pad can be connected to a telemetryunit of the device. The telemetry unit can be configured to wirelesslycarry electrical signals between the interface pad and a non-implantedrecording or stimulating apparatus of the device.

For any such embodiments of the implantable microelectrode body theamorphous silicon carbide insulation can include a first amorphoussilicon carbide layer and a second amorphous silicon carbide layer. Thethin film metal and the interface pad can lay on the first amorphoussilicon carbide layer and the second amorphous silicon carbide layer cancover the thin film metal and some or all of the first amorphous siliconcarbide layer. The opening in the amorphous silicon carbide insulationcan be through the second amorphous silicon carbide layer to therebyexpose the interface pad to the ambient environment. For some suchembodiments, the neural interface probe can further include a secondthin film metal trace connected to a second interface pad.

For some such embodiments, the second thin film metal trace and thesecond interface pad can be located on the first amorphous siliconcarbide layer and the second amorphous silicon carbide layer can coverthe thin film metal and some or all of the first amorphous siliconcarbide layer. The second thin film metal trace and the second interfacepad can be laterally separated from the first thin film trace and thefirst interface pad that are located on the first amorphous siliconcarbide layer. The opening in the amorphous silicon carbide insulationcan include discrete openings through the second amorphous siliconcarbide layer to thereby expose the first interface pad and the secondinterface pad to the ambient environment.

Additionally or alternatively, for some such embodiments, the secondthin film metal trace and the second interface pad can be located on thesecond amorphous silicon carbide layer and a third amorphous siliconcarbide layer of the amorphous silicon carbide insulation can cover thesecond thin film metal trace. The second thin film metal trace and thesecond interface pad can be laterally and vertically separated from thethin film trace and the interface pad located on the first amorphoussilicon carbide layer. The opening in the amorphous silicon carbideinsulation can include discrete openings through the second amorphoussilicon carbide layer and through the third amorphous silicon carbidelayer to thereby expose the first interface pad and the second interfacepad to the ambient environment.

Any embodiments of the neural interface probe can further include aplurality of thin film metal traces located on any of a plurality ofamorphous silicon carbide layers. At least one of the thin metal tracesis exposed to the ambient environment through an opening in one or moreof the amorphous silicon carbide layers.

Any embodiments of the implantable microelectrode body can furtherinclude a plurality of the neural interface probes.

Another embodiment of the present invention is a method of manufacturingthe neural interface device that comprises forming a neural interfaceprobe of an implantable microelectrode body. Forming the neuralinterface probe can include plasma enhanced chemical vapor deposition ofa first amorphous silicon carbide insulation layer, and forming a thinfilm metal trace and interface pad on the first amorphous siliconcarbide insulation layer, wherein the interface pad is formed on aportion of the thin film metal trace. Forming the neural interface probecan include plasma enhanced chemical vapor deposition of a secondamorphous silicon carbide insulation layer on the first amorphoussilicon carbide insulation layer and covering the thin film metal traceand the interface pad, and forming an opening in the second amorphoussilicon carbide insulation layer to expose the interface pad to anambient environment. Forming the neural interface probe can includepatterning the first and second amorphous silicon carbide insulationlayer to define the neural interface probe, including any of theembodiments of the neural interface probe of the above-disclosed neuralinterface device.

In any such embodiments of the method, the plasma enhanced chemicalvapor deposition conditions of the first and second amorphous siliconcarbide insulation layers and the formation conditions of the thin filmmetal trace and the interface pad can be selected such that intrinsicstresses in the first and second amorphous silicon carbide insulationlayers are offset by residual stresses in the thin film metal trace andthe interface pad, such that the neural interface probe has asubstantially neutral stress. In some such embodiments, the plasmaenhanced chemical vapor deposition conditions of the first and secondamorphous silicon carbide insulation layers includes a temperature in arange from about 200 to about 400° C., a deposition pressure in a rangefrom about 800 to about 1200 millitorr, a reactive gas mixture comprisedof silane (SiH₄) and methane (CH₄), with a molar compositional ratio(SiH₄:CH₄) in a range from about 1:2 to about 2:1, a carrier gas ofargon, and a total flow rate of the reactive gas mixture plus thecarrier gas in a range from about 600 to about 1200 sccm. In some suchembodiments, the formation conditions of the thin film metal trace andthe interface pad includes a physical vapor deposition process that caninclude sputtering with an inert gas plasma at a pressure in a rangefrom about 1 and 40 about millitorr, or, thermal evaporation at anambient deposition temperature. In some such embodiments, each of thefirst and the second amorphous silicon carbide insulation layers canhave a thickness in a range from about 0.1 to about 4 microns, and eachof the first and the second amorphous silicon carbide insulation layerscan have a compressive residual stress in a range from about 50 to about200 MPa. In some such embodiments, the thin metal trace can have athickness in a range from about 0.1 and about 2 microns, and the thinmetal traces can have a residual stress in a range from about 100 MPa incompression to about 500 MPa in tension.

BRIEF DESCRIPTION

Reference is now made to the following descriptions taken in conjunctionwith the accompanying drawings, in which:

FIG. 1 is a plan view of an example embodiment of a microelectrode body(100) comprising a neural interface probe (105), a thin film metal trace(110), an interface pad (115) defined by a first opening in an amorphoussilicon carbide layer (135), a connection body (120), an electricalcontact pad (125) defined by a second opening in the amorphous siliconcarbide, and a distal tip (130) at the terminus of the neural interfaceprobe (105) defined by an included angle of less than 90 degrees);

FIG. 2 is a perpendicular cross-sectional view of the neural interfaceprobe (105) of FIG. 1 and taken at the section indicated in FIG. 1 (900)showing a thin film metal trace (110) completely surrounding by a-SiC(135);

FIG. 3 is an embodiment of the implantable microelectrode body (100)comprising four neural interface probes (105) in contact with aconnection body (120) wherein each neural interface probe is configuredto have a neural interface pad (115) defined by an opening in an a-SiClayer (135);

FIG. 4 is an embodiment of the implantable microelectrode body (100)comprising four neural interface probes (105) in contact with aconnection body (120) wherein two neural interface probes are configuredto have a neural interface pad (115) defined by an opening in an a-SiClayer (135);

FIG. 5 is an embodiment of the implantable microelectrode body (100)comprising six neural interface probes (105) in contact with aconnection body (120) wherein the neural interface probes are configuredto have more than one length, each neural interface probe optionallyhaving a neural interface pad (115) defined by an opening in an a-SiClayer (135);

FIG. 6 is an embodiment of the invention showing a neural interfaceprobe (105) with a distal tip (130) extended to a point symmetricallyabout a centrally positioned longitudinal axis (902) of the probe anddefined by the convergence of two approximately rectangular sides (140)of the probe tip;

FIG. 7 is an embodiment of the invention showing a neural interfaceprobe (105) with a distal tip (130) extended to a point asymmetricallyabout a centrally positioned longitudinal axis (902) of the probe anddefined by the convergence of two approximately rectangular sides (140)of the probe tip;

FIG. 8 shows an example embodiment (100) of the present invention havinga plurality of neural interface probes (105) in contact with aconnection body (120) wherein the neural interface probes have ageometric configuration in which the longitudinal axis of the probes isadvantageously curved in a direction away from the center line (905) ofthe implantable microelectrode body (100;

FIG. 9 shows an example embodiment of the implantable microelectrodebody (100) wherein an interface probe (105) is configured to have aplurality of neural interface pads (115) defined by a first set openingsin an a-SiC layer (120), the interface pads in contact with one or aplurality of metal traces (for clarity not shown) in contact with aplurality of electrical contact pads (125) defined by a second set ofopenings in an a-SiC layer (120);

FIG. 10 is an example embodiment related to the implantablemicroelectrode body (100) described FIG. 9, showing a perpendicularcross section located at (900) of the neural interface probe (105)having thin film metal traces (110) completely surrounding by a-SiC(135);

FIG. 11 is an example embodiment of the implantable microelectrode bodyof the present invention (100) having a plurality of interface pads(115) defined by a first set of openings in an a-SiC layer (135) whereinthe interface pads are in contact with at least one fewer thin filmmetal traces (110), the thin film metal traces extending to a connectionbody (120) having electrical contact pads (125) defined by a second setof openings in an a-SiC layer (135).

FIG. 12 is an example embodiment of the implantable microelectrode bodyof the present invention (100) having a plurality of neural interfaceprobes (105) in contact with a connection body (120), the neuralinterface probes having interface pads (115) defined by a first set ofopenings in an a-SiC layer (135), the interface pads being in contactwith at least one fewer thin film metal traces (110), a least one thinfilm metal trace being disposed on a plurality of neural interfaceprobes, the thin film metal traces extending to a connection body (120)having electrical contact pads (125) defied by a second set of openingsin an a-SiC layer (135).

FIG. 13 shows a plan view and a perpendicular cross-sectional viewlocated at (900) of an example embodiment of the invention wherein aninterface pad (115) is coated with an electrode material (145), a firstsurface of the electrode material in contact with a thin film metaltrace (110) and a second surface of the electrode material in contactwith the ambient;

FIG. 14 shows a plan view and a perpendicular cross-sectional viewlocated at (900) of an example embodiment of the invention wherein aninterface pad (115) is coated with an electrode material (145), a firstsurface of the electrode material in contact with a thin film metaltrace (110) and with a surface of the a-SiC (135) and a second surfaceof the electrode material in contact with the ambient;

FIG. 15 is an example embodiment of a neural microelectrode body (100)having eight neural interface probes (105), each neural interface probehaving an interface pad (110) in contact with a metal trace (110), themetal trace extending to a distant connection body (120);

FIG. 16 is a diagrammatic overview of the fabrication of an embodimentof the present invention;

FIG. 17 is an optical photograph of an example embodiment of animplantable microelectrode body showing a separation between neuralinterface probes (105) and a connection body (120);

FIG. 18 is a magnified optical image of the distal end of theimplantable microelectrode body showing bundling of neural interfaceprobes (105) to form a monolithic structure with increased resistance tobuckling during implantation;

FIG. 19 is a magnified optical image of an embodiment of the presentinvention having neural interface probes (105) with a length of about 4mm suitable for implantation into brain;

FIG. 20 is a magnified optical image of the embodiment shown in FIG. 19,further configured with an electrical connector (185) attached toelectrical contact pads on the connection body (120) using solder joints(190); and

FIG. 21 is an embodiment of the present invention showing a plurality ofneural interface devices (100) in a stacked arrangement, wherein theindividual neural interface devices are separated by a spacer (195) toform a monolithic structure useful for interfacing with athree-dimensional volume of tissue.

DETAILED DESCRIPTION

As part of the present invention is our recognition that neuralinterface probes whose principle material of construction is composed ofamorphous silicon carbide (a-SiC) insulation possess several desirablecharacteristics. Making such probes principally out of a-SiC allows themanufacture of a probe with a small enough cross-sectional area tominimize foreign body response, but still provide enough bucklingresistance to reduce undesirable buckling, when implanted into tissue.Additionally, providing a probe whose outer surface is substantiallyentirely composed a-SiC (e.g., at least about 90 percent of the outersurface) provides an excellent barrier against biological fluids thatcould corrode metal thin film traces of the probe and cause a decline indevice performance.

The neural interface devices of the present invention employ amorphoussilicon carbide. Amorphous silicon carbide is distinguished from otherforms of silicon carbide by not exhibiting crystallinity when analyzedby x-ray diffraction. Prior art devices discloses the use ofpolycrystalline silicon carbide in the construction of devices intendedfor interfacing to neural tissue. Diaz-Botia et al., 2017 teach the useof crystalline silicon carbide in a geometry that disposes electrodesites in a planar configuration on the surface of a neural tissuetarget. Polycrystalline silicon carbide is formed at high temperaturesby low pressure chemical vapor deposition and is n-doped andconsequently has electronic conductivity. The high depositiontemperature and electronic conductivity make n-type silicon carbideunsuitable for fabrication of the neural interface probes of the presentinvention. Frewin et al., (WO 2013/010161 A2) disclose a long-termimplantable neural interface device employing crystalline siliconcarbide (3C-SiC) wherein the cubic silicon carbide is employed as a basematerial in an electrolyte insulator semiconductor capacitor and as abase material in a field effect transistor. Diaz-Botia et al., 2017,employ amorphous silicon carbide as an insulating encapsulation layerfor metal traces in their neural interface probes. Similarly, Lei etal., 2016 describe the use of amorphous silicon carbide as a protectivecoating for neural interface devices placed in contact with retinalneural tissue; Cogan et al., 2003 describe the use of amorphous siliconcarbide as an insulating coating for microelectrodes that are implantedinto neural tissue; and Cogan, U.S. Pat. No. 5,755,759 describes the useof amorphous silicon carbide in combination with amorphous siliconoxycarbide as a high electronic resistivity coating for a neuralinterface probe. None of the aforementioned Prior Art referencesdescribe the use of amorphous silicon carbide as the predominantmaterial of construction of an neural interface probe and, further, donot describe neural interface probes employing amorphous silicon carbidein a geometry that advantageously allows the implantation of neuralinterface probes into neural tissue, or other tissues, wherein theneural interface probes have a geometry that substantial avoids anadverse foreign body response.

One embodiment of the disclosure is a neural interface device. FIG. 1presents a plan view of an example embodiment of the device (100). Thedevice comprises a neural interface probe (105) which is implanted intothe neural tissue from which neural electrical activity is recorded orneural activity electrically stimulated. An interface pad (115) isdefined on the neural interface probe by an opening in an a-SiC layer(135). The interface pad has the property of being electronicallyconducting and provides an electrical connection to the neural tissue ofthe ambient environment. The length of the neural interface probe andthe position of the interface pad along the longitudinal axis of theneural interface probe are chosen to place the interface pad at alocation in the ambient advantageous for neural recording andstimulation. To facilitate the implantation of the neural interfaceprobe into tissue, the distal tip (130) of the probe is configured witha point capable of penetrating into tissue with minimal force. In oneembodiment, the distal tip is defined by two rectangular sides of theneural interface probe that intersect at the distal tip with an includedangle of 90 degrees or less. In a related embodiment, the distal tip maybe configured to have a radius of curvature. The radius of curvature isless than or equal to one half the width of the neural interface probe.It is possible to combine these embodiments. The thin film metal trace(110) extends from the interface pad to a connection body (120).Electrical connection to the implantable microelectrode device can bemade at the connection body by creating an opening in an a-SiC layer toform an electrical contact pad (125).

The term rectangular cuboid shape as used herein refers to asubstantially box-shaped structure defined in three dimensional space bya length (corresponding to the long axis), a breadth (corresponding tothe horizontal width) and height (corresponding to the thickness) of theprobe with the exception in some embodiments of the insertion end of theprobe which can be tapered to facilitate tissue insertion. The faces ofthe rectangular cuboid shaped probe are substantially planar.

The term amorphous silicon carbide refers to a silicon carbide structurethat is substantially devoid of crystal structures such as indicated byan x-ray diffraction scan that would not show discrete sharp peaks ofscattered radiation corresponding to crystalline or crystallite forms ofsilicon carbide. For example, substantially the entire (e.g., at leastabout 99% percent) x-ray diffraction spectrum of an a-SiC structure ofthe disclosure may have no x-ray diffraction peaks with a full width athalf maximum of less than about 5 degrees in diffraction angle.

In an embodiment of the invention directed to facilitating theimplantation of amorphous silicon carbide neural interface probes intotissue, the neural interface probe is configured to resist buckling asit traverses through tissue. While enabling passage of the probe throughtissue, the configuration advantageously preserves cross-sectionaldimensions of the probe that minimize insertion trauma and foreign bodyresponse. The desirable properties of buckling resistance and minimizingforeign body response present conflicting requirements on thecross-sectional dimensions and stiffness of a neural interface probe.Buckling resistance may be achieved by increasing cross-sectionaldimensions of the neural interface probe whereas minimizing insertiontrauma and foreign body response may be achieved by decreasing thecross-sectional dimensions of the neural interface probe. Without regardto the length of the neural interface probe, the buckling resistance ofa probe is proportional to the elastic modulus (E) of the probe in itslongitudinal dimension multiplied by the smallest area-moment-of-inertiaof the probe cross-section (I). In the present embodiment, the probe isconfigured with an approximately rectangular cross-section with basedimension b and height dimension h, the height dimension h being lessthan or equal to the base dimension b. The smallestarea-moment-of-inertia is then given by the well-known formula,

$I = \frac{{bh}^{3}}{12}$

To minimize insertion trauma and the foreign body response, it isdesirable to a have at least one cross-sectional dimension of the probeless than 10 micrometers. Thus, for a neural probe of approximatelyrectangular cross-section, h is desirably less than 10 micrometers.Skilled artisans will understand that the fabrication of thin filmsdevices comprising multiple patterned layers often results incross-sectional geometries that are often trapezoidal. A rectangularcross sectional geometry is used for illustration without limitation.

An advantage of the rectangular cross-section compared with the circularcross-section employed in Prior Art carbon fiber electrodes is thehigher area moment of inertia of the rectangular cross-section for thesame minimum cross-sectional dimension. By way of example, a rectangularneural interface probe with h=5 micrometers has a minimum area moment ofinertia of 52 □m⁴ when b=5 micrometers. A circular neural probe with anequivalent minimum cross-sectional dimension has an area moment ofinertia of 31 □m⁴. Thus for a fixed minimum cross-sectional dimension,the area moment of inertia of the rectangular cross-section is higher,imparting the desirable property of increased buckling resistance.Likewise, comparing a neural probe with a rectangular cross-section witha probe having a circular cross-section, both having the same areamoment of inertia, the rectangular probe has a minimum cross-sectionaldimension that is less than or equal to 88% that of the circular probe.The smaller cross-sectional dimension of the rectangular probeadvantageously reduces the foreign body response.

The foregoing discussion teaches an advantage of a neural probe with arectangular cross section for increasing buckling resistance whileminimizing tissue damage. A further increase in buckling resistance isobtained by configuring the cross-section of the probe to comprisesubstantially of a high-elastic-modulus material. A further advantage isobtained if the high elastic modulus material is disposed on theperimeter of the probe cross-section. The present invention is directedto the use of amorphous silicon carbide as the high elastic modulusmaterial. Amorphous silicon carbide has a modulus of elasticity ofapproximately 300 GPa. Skilled artisans will appreciate that the modulusmay vary depending on the method and process parameters used in thepreparation of the amorphous silicon carbide. Since the bucklingresistance is proportional to the EI product, an amorphous siliconcarbide probe with a rectangular cross section having dimensions b=h=5micrometers will have a buckling resistance proportional to 15.6 N-□m².In a preferred embodiment of the invention, therefore, the amorphoussilicon carbide neural interface probe has an EI product of 15.6 N-□m²or larger with at least one cross-sectional dimension less than 10 □m.Skilled Artisans will understand that the contribution of the metaltrace or traces within the neural interface probe may also influence theEI product. Metals used in the construction of the traces have a lowermodulus of elasticity than amorphous silicon carbide, which has theeffect of decreasing the EI product of the probe. Consequently, thecross-sectional dimensions of an interface probe having a multiplicityof metal traces may be increased to achieve a desired EI product whilepreserving the constraints that at least one cross-sectional probedimension is less than 10 □m and the EI product is 15.6 N-□m² orgreater.

A useful feature of the neural interface probe of the present inventionis a high degree of planarity. Planarity is the property of the neuralinterface probe that the upper and lower surfaces of the probe areco-planar and that each of these surfaces lie within a plane. Theplanarity of the probe is advantageous in minimizing tissue damageduring implantation. It is commonly understood that thin films ofmaterials fabricated by the processes employed in the fabrication of theneural interface probes have intrinsic residual stresses. If thesestresses are unbalanced or non-uniformly distributed within the neuralinterface probe, a deflection of the probe occurs with consequent lossof planarity. In amorphous silicon carbide these residual stresses aretypically compressive. Carefully selection of deposition conditions forthe formation of the amorphous silicon carbide is required to minimizethese stresses. Advantageously for the fabrication of the neuralinterface probes, the amorphous silicon carbide has an intrinsic stressbetween −50 MPa and −150 MPa, where the minus sign indicates acompressive stress state. The metal traces used in the fabrication ofthe interface probes also contain residual stresses. An inventivefeature of the neural interface probes is the control of residual stresswithin the metal traces and selection of the area-fraction of the metalwithin the probe cross-section to balance the compressive stress withinthe amorphous silicon carbide. Therefore, in an embodiment of theinvention the metal traces have a tensile residual stress and areconfigured to have a cross-sectional area and position within the shankcross-section such that the bending moment about the neutral axis of theprobe is minimized and sufficient planarity is retained to permitimplantation into tissue.

As part of the present invention, it is recognized that an implantablemicroelectrode body with a plurality of neural interface probes hasdesirable characteristics. The plurality of interface probes increasesthe number of neural interface pads in contact with the ambient andallows control of the spatial distribution of the contact pads in theambient. One embodiment of the present invention having a plurality ofneural interface probes (105) is shown in perspective view in FIG. 3.The implantable microelectrode body (100) is shown with four neuralinterface probes. Typically, each neural interface probe will have oneor a plurality neural interface pads (115) distributed along thelongitudinal axis of the probe. In some aspects of the presentembodiment (FIG. 4), one or more of the plurality of neural interfaceprobes (105) is configured without a neural interface pad. Neuralinterface probes without a neural interface pad are desirable for thepurpose of stabilizing an implantable microelectrode body on the surfaceof the implanted tissue.

In a related embodiment of an implantable microelectrode device with aplurality of neural interface probes shown in FIG. 5, the longitudinallength of the individual neural interface probes is selected tofavorably distribute the neural interface pads (115) over a range ofdepths in the ambient. Without limitation, advantageous lengths of theneural interface probes may range from about 0.05 mm to 20 mm. Neuralinterface probes with a length from 0.05 mm to about 4 mm areparticularly suited to peripheral nerve implantation. Neural interfaceprobes with a length from about 0.5 mm to 20 mm are particularly suitedto cortical implantations and to implantation in deep brain structures.

In as aspect of the invention related to any embodiment, the distal tip(130) of a neural interface probe (105) has a geometry suitable forpenetrating tissue. The distal tip is located at the terminus of theneural interface probe at its greatest distance from the connection body(120). A suitable geometry includes a distal tip defined by twoapproximately rectangular sides (140) of the neural interface probe thatsymmetrically converge about a center line (900) to a point with anincluded angle of less than about 90 degrees and more preferably lessthan about 20 degrees.

In an aspect of the invention related to the geometry of the distal tipof a neural interface probe (105), the sides (140) of the neuralinterface probe at the distal tip converge asymmetrically as shown inFIG. 7. The included angle between the convergent sides remains lessthan 90 degrees and preferably less than 20 degrees. A tip thatconverges asymmetrically may be used advantageously to direct the pathtaken by the neural interface probe as it traverses through tissueduring implantation. The neural interface probe is deflected in adirection opposite to the rectangular side of the neural interface probetip presenting the largest surface area projected in the direction ofmotion of the probe.

In an embodiment of the invention related to methods of implantation,the neural interface probes have a geometric configuration in which thelongitudinal axis of the probes is advantageously curved in a directionaway from the center line (905) of the implantable microelectrode body(100) as shown in FIG. 8 in plan view. In FIG. 8, the present embodimentis shown having eight neural interface probes (105) with intrinsiccurvature. As described for Prior Art carbon fiber electrodes (Gardneret al., U.S. application Ser. No. 14/902,734), when an implantablemicroelectrode body with a plurality of neural interface probes iswithdrawn from water, the neural interface probes form a bundle in whichthe neural interface probes are weakly held together by van der Waalsbonding. The bundle has a higher stiffness than an individual neuralprobe allowing penetration of the probe bundle into tissue duringimplantation without buckling of the bundle. As described in Gardner etal (U.S. application Ser. No. 14/902,734), the individual neural probeswithin a bundle will splay into tissue during implantation causing theinterface pads to be distributed advantageously in a three-dimensionalvolume of tissue. In the present embodiment, a similar bundling andsplaying behavior has been observed with amorphous silicon carbideneural interface probes. In contrast to Gardner et al., we havediscovered that amorphous silicon carbide probes with intrinsiccurvature will also form a bundle weakly held together by van der Waalsbonding. The intrinsic curvature of the amorphous silicon carbide isadvantageous in promoting splaying of the neural probes as they traversetissue during implantation. A shortcoming of Prior Art implantabledevices based on carbon fiber electrodes is the inability to fabricateneural probes from carbon fiber having intrinsic curvature.

In an embodiment of the present invention desirable for enhancing thespatial selectivity of neural recording and stimulation, a neuralinterface probe is configured to have a plurality of interface pads. Aplan view of a neural interface probe (105) of the present embodimenthaving four interface pads (115) is shown in FIG. 9. Each interface pad(115) may be in contact with a metal trace also in contact with theamorphous silicon carbide insulation. Each interface pad may beconnected to the ambient through an opening in the amorphous siliconcarbide insulation. In some embodiments, thin film metal traces of theneural interface probe can extend to a communication circuit of theconnection body (120), and, the communication circuit can include anelectrical contact pad directly connected to the thin film metal trace.A perpendicular cross-sectional view of a neural interface probe of thepresent embodiment having four interface pads is shown in FIG. 10. Inpreferred embodiments, the number of interface pads on a neuralinterface probe may be in the range two to 16.

In an embodiment shown in FIG. 11 and advantageous in neuralstimulation, two or more interface pads on a neural interface probe canbe in contact with a common thin film metal trace. The thin film metaltrace can extend to a communication circuit on the connection body. In arelated embodiment shown in FIG. 12, an implantable neural interfacedevice with a plurality of neural interface probes is configured to havea plurality interface pads on a plurality of the neural interface probeswherein the thin metal traces in contact with interface pads areelectrically connected at a communication circuit of the connectionbody.

In an embodiment advantageous for neural stimulation and recording,shown in FIG. 13, the interface pad (115) is configured to be in contactwith an electrode material (145) having desirable properties forstimulating and recording neural activity. The electrode material isfurther in contact with the ambient. Without limitation, such electrodematerials include titanium nitride, iridium oxide, platinum, iridium,platinum-iridium alloy, palladium, and poly(ethylenedioxythiophene). Ina related embodiment shown in FIG. 14, the electrode material (145)extends from the interface pad onto a portion of the surface of theamorphous silicon carbide (135) exposed to the ambient. A metal layersuitable for promoting adhesion may be disposed between the electrodematerial and the interface pad or between the electrode material and theamorphous silicon carbide insulation. Preferred metals for the adhesionpromoting layer include, titanium, chromium, tungsten, andtitanium-tungsten alloys.

In an embodiment of the invention, the connection body is configured tohave an elongated structure in which the thin film metal trace or tracesextend in the direction of the long axis of the connection body to adistant communication circuit. The elongated structure is advantageouslyconfigured to have flexibility in at least one direction perpendicularto the long axis of the connection body. A representative plan view ofthe present embodiment is shown in FIG. 15. This embodiment isadvantageous in causing the connection circuit to be placed at adistance from the implantation site of the neural interface probes. Suchadvantages may include, without limitation, the ability to use largetelemetry devices on the connection body without interfering with thefunction of the neural tissue or the ability to place the communicationcircuitry outside the body without the use of a telemetry device orwithout the need for implanted electrical connections between a wire orribbon cable and the communication circuitry.

In an embodiment of the invention shown in FIG. 21, useful forinterfacing to a three-dimensional volume of tissue, a plurality ofneural interface devices (100) are configured in a parallel orientationwith the connection bodies (120) of the neural interface devices in aface-to-face orientation. The connection bodies of the interface devicesare separated by a solid spacer (195). The contacting surfaces of thespacer (195) and the connection bodies (120) are adhesively bonded withan epoxy, acrylic, or other bonding agent suitable for chronicimplantation. In related embodiments the neural interface devices (100)may individually employ one or a plurality of neural interface probes(105); the neural interface probes may individually employ one or aplurality of interface pads (115), such interface pads being defined byopenings in an amorphous silicon carbide layer of the neural interfaceprobe and being connected to connection pads (125) by metal traces (notshown). There is no restriction on the number of neural interfacedevices that may be assembled in the manner shown in FIG. 21. Preferredembodiments employ from two to ten neural interface devices. The neuralinterface probes (105) of the present embodiment may be of differentlengths and may be positionally offset between neural interface devices.Such positional offset allowing the neural interface probes to deflectout of the plane of the neural interface device without interfering withthe neural interface probes on adjacent interface devices. Allpreviously described embodiments of the neural interface devices arecontemplated for use in the embodiment described in FIG. 21. Thethickness of the spacer (195) separating individual neural interfacedevices may vary from about 0.005 mm to 1 mm. The spacers may befabricated from many different materials suitable for implantableapplications including polymers, metals, and ceramics. Preferredmaterials for the spacers include epoxy photoresists such as SU-8, whichis well-known in the fabrication of implantable devices, alumina andpolyimide.

As illustrated in FIG. 21, embodiments of neural interface device canfurther comprising a plurality of the implantable microelectrode bodies100 a, 100 b, at least two of the implantable microelectrode bodies eachhaving at least one of the neural interface probes 105. Each of theimplantable microelectrode bodies 100 a, 100 b can further include aconnection body (e.g., 120 a, 120 b respectively) surrounded by theamorphous silicon carbide insulation (e.g., a-SiC 135, FIG. 1). Each ofthe implantable microelectrode bodies 100 a, 100 b can be stacked in aface-to-face orientation such that a major plane of each of theconnection bodies 120 a, 120 b (e.g., major planes 122 a, 122 b,respectively) are parallel to each other and the connection bodies 120a, 120 b are separated from each other by one or more solid spacerlayers 195.

Example 1

The following example describes the fabrication of an exampleimplantable microelectrode body of the type shown in FIG. 15. In theexample embodiment, the device has 8 neural interface probes (105)connected to a communication circuit on a connection body (120). Theconnection body is separated from the neural interface probes by adistance of approximately 50 mm. Referring to FIG. 16, in a first step,a single crystal wafer of silicon (150) with a diameter of 100 mm, iscoated with a thin film of polyimide (155) having a thickness of about 1micron. The polyimide layer is applied to the wafer by spin coating apolyimide precursor solution onto the wafer and curing the precursor at350° C. for one hour in a nitrogen atmosphere to form the polymerizedpolyimide coating. In a second step, a first layer of amorphous siliconcarbide (160) having a thickness of about 2 microns is then depositedover the polyimide layer by plasma enhanced chemical vapor deposition(PECVD) at a substrate temperature of 325° C., RF power density of 0.20Wcm² (13.56 MHz), and pressure of 1000 millitorr using a reactive gasmixture of silane (SiH₄) and methane (CH₄) at flow rates of 12 sccm and36 sccm respectively. The total gas flow rate into the PECVD reactionchamber is maintained at 800 sccm using argon as a carrier gas. In athird step, thin film metal traces (165) are formed on the firstamorphous silicon layer by sputter deposition using lift-offphotolithography to define the metal pattern. To facilitate liftoff, anon-photosensitive resist layer, known as lift off resist and aphotosensitive resist layer are spin-coated consecutively on the firstamorphous silicon carbide layer in a process designed to create anundercut in the two-layer resist. The two-layer resist is then exposedto ultraviolet radiation through a first photomask that defines thepattern of the metal traces on the neural interface probe and on theconnection body of the device. The metal layer is deposited by DCsputtering and comprises a three-layer coating of titanium, gold, andtitanium with respective thicknesses of 30 nm, 250 nm, and 30 nm. Aftermetal deposition, the coated silicon wafer is immersed in a solutionsuitable for removing the resist layers and unwanted metal layers tocreate the desired thin film metal pattern. In a fourth step, a secondlayer of amorphous silicon carbide (170) having a thickness of about twomicrons is deposited over the metal traces and the first amorphoussilicon carbide layer to provide complete insulation of the metal traceswithin amorphous silicon carbide. In a fifth step, openings (175) areformed in the second amorphous silicon carbide layer to expose theinterface pads to the ambient and, on the connect body (120) of FIG. 15,to form openings for electrical contact pads (125) of FIG. 15. Theinterface pads are an integral part of the thin film metal layer (110)and the shape and size of the interface pad is determined by the shapeand size of the opening in the second amorphous silicon carbide layer.The openings in the second amorphous silicon carbide layer are createdby reactive ion etching (RIE) in a sulfur hexafluoride (SF₆) plasma at apressure of four millitorr using an inductively coupled plasma (ICP)etcher. In the present devices, the openings for the interface pads are2 microns by 50 microns resulting in an interface pad area of 100micron². The etching of the second amorphous silicon carbide layer waslimited to the interface pads and the electrical contact pads using alayer of photoresist patterned by exposure to ultraviolet light througha second photomask. In a sixth step, the external shape of theimplantable microelectrode body is defined by removing all of the firstand second amorphous silicon carbide layers that are not a desired partof the implantable body using a second reactive ion etching step in apattern defined by a third photomask. In a seventh step, the coatedsilicon wafers are immersed in deionized water at 87° C. until theimplantable microelectrode body (180) releases from the silicon wafer.Optionally, the released implantable microelectrode bodies are exposedto an oxygen plasma to remove the layer of polyimide in contact with thefirst silicon carbide layer. An optical image of an implantablemicroelectrode of Example 1 is shown in FIG. 17. The microelectrodecomprises eight neural interface probes (105) connected to a connectionbody (120). The distal tip of each neural interface probe terminates ina symmetric triangular tip with an included angle of 10 to 14 degrees.Each neural interface probe has a thin metal trace (110) that extendsfrom an interface pad near the distal tip of the neural probe to anelectrical contact pad on the connection body. The geometric arrangementof electrical contact pads on the connection body is configured to alignwith contact pads on an electrical connector. Referring to FIG. 18,which is a magnified optical image of the distal tip of the implantablemicroelectrode body shown in FIG. 17, the neural interface probes (105)are formed into a bundle held together by van der Waals bonding. In astated embodiment of the invention, the bundle is advantageous inminimizing buckling of the neural interface probes during implantationinto tissue.

Example 2

Following the process outlined in Example 1, an implantablemicroelectrode body (100) having 16 neural interface probes (105), eachof length 4 mm and suitable for implantation in brain, was fabricated.An optical image of the implantable microelectrode body is shown in FIG.19. Each neural interface probe (105) is configured to have an interfacepad (not shown) in contact with a thin film metal trace (110) extendingto a connection body (120). At the connection body, the metal trace isconnected to an electrical contact pad (125). In the present Example,electrical contact pads are configured to match with an electricalconnector (185) suitable for interfacing with electronic equipmentsuitable for neural recording and stimulation. The electrical connectoris mounted on the connection body (120) by solder joints (190) betweenthe metal conductors on the connector to the electrical contact padsexposed by openings in the second silicon carbide layer.

Example 3

Referring to FIG. 1, the present example demonstrates a feature of theimplantable neural interface device (100) that is advantageous forinsertion of neural interface probes (105) of the neural interfacedevice into tissue. Using the PECVD and RIE methods described in Example1, an amorphous silicon carbide neural interface probe (105) withtransverse cross-sectional dimensions of 6 microns by 8 microns and aprobe length of 2 mm was fabricated. The neural interface probe (105)thus has a transverse cross-sectional area of 48 microns. The connectionbody of the neural interface probe is attached to an apparatus thatprovides insertion of the neural interface probe into brain at acontrolled speed. The apparatus further measures the force required toinsert the neural interface probe into tissue. The probe was insertedinto the exposed brain of a rat to a depth of approximately 1.5 mmwithout buckling. The force to penetrate the surface of the rat brainwas determined to be 0.35 mN and the maximum force recorded duringinsertion was 1.5 mN.

Those skilled in the art to which this application relates willappreciate that other and further additions, deletions, substitutionsand modifications may be made to the described embodiments.

What is claimed is:
 1. A method of manufacturing neural interfacedevice, comprising: forming a neural interface probe of an implantablemicroelectrode body, including: plasma enhanced chemical vapordeposition of a first amorphous silicon carbide insulation layer;forming a thin film metal trace and interface pad on first amorphoussilicon carbide insulation layer, wherein the interface pad is formed ona portion of the thin film metal trace; plasma enhanced chemical vapordeposition of a second amorphous silicon carbide insulation layer on thefirst amorphous silicon carbide insulation layer and covering the thinfilm metal trace and the interface pad; forming an opening in the secondamorphous silicon carbide insulation layer to expose the interface padto an ambient environment; patterning the first and second amorphoussilicon carbide insulation layer to define the neural interface probe,wherein: the probe has a rectangular cuboid shape, a cross-sectionalarea perpendicularly transverse to a long axis length of the probe andthrough any perpendicularly transverse cross-section along the long axislength is less than about 50 microns, and the amorphous silicon carbideinsulation layers are the principle material of construction of theprobe such that at least about 85 percent of a total area any one of thecross-sections along the long axis length is composed of the amorphoussilicon carbide insulation layers.
 2. The method of claim 1, wherein theplasma enhanced chemical vapor deposition conditions of the first andsecond amorphous silicon carbide insulation layers and the formationconditions of the thin film metal trace and the interface pad areselected such that intrinsic stresses in the first and second amorphoussilicon carbide insulation layers are offset by residual stresses in thethin film metal trace and the interface pad, such that the neuralinterface probe has a substantially neutral stress.
 3. The method ofclaim 1, wherein: the plasma enhanced chemical vapor depositionconditions of the first and second amorphous silicon carbide insulationlayers includes: a temperature in a range from about 200 to about 400°C., a deposition pressure in a range from about 800 to about 1200millitorr, a reactive gas mixture comprised of silane (SiH₄) and methane(CH₄), with a molar compositional ratio (SiH₄:CH₄) in a range from about1:2 to about 2:1, a carrier gas of argon, and a total flow rate of thereactive gas mixture plus the carrier gas in a range from about 600 toabout 1200 sccm; and the formation conditions of the thin film metaltrace and the interface pad includes a physical vapor deposition processincluding: sputtering with an inert gas plasma at a pressure in a rangefrom about 1 and 40 about millitorr, or, thermal evaporation at anambient deposition temperature.
 4. The method of claim 1, wherein eachof the first and the second amorphous silicon carbide insulation layershave a thickness in a range from about 0.1 and about 4 microns, and eachof the first and the second amorphous silicon carbide insulation layershave a compressive residual stress in a range from about 50 to about 200MPa.
 5. The method of claim 1, wherein: the thin metal trace has athickness in a range from about 0.1 and about 2 microns, and the thinmetal traces have a residual stress in a range from about 100 MPa incompression to about 500 MPa in tension.